The long-range goal of this project is a comprehensive study of the effects of hypoxia on central nervous tissue of mammals. Since the objective is the effect of oxygen deprivation, separated from indirect effects caused by systemic changes, in vitro preparations are used in many experiments. Recordings from the brains of anesthetized rats will be used to compare effects observed in vitro to the responses of brain in situ. Cerebral hypoxia leads to: I. reversible failure of synaptic functions; II. irreversible loss of function; III. delayed deterioration after initial recovery following reoxygenation. A set of hypotheses has been developed, in part from the literature, and in part from the results of past work in our laboratory concerning the mechanism of this sequence of processes. This proposal is for the testing of key elements of the hypothetical hypoxic process. Experiments planned for this budget period fall into six sub-projects: 1.Hypoxic conduction failure in spinal presynaptic terminals in isolated mouse spinal cord. 2.The changes of EPSP, threshold, membrane potential and membrane current in the reversible phase of hypoxia in hippocampal tissue slices. 3.Intracellular recordings during and after hypoxic and normoxic spreading depression (SD) in hippocampal tissue slices. 4.Reversibility of prolonged, K+-induced SD in cerebral cortex and in hippocampus in the brain of anesthetized rats. 5.Comparison of hypoxic changes in CA1, CA3 and in fascia dentata (FD) of the brain of anesthetized rats. 6.Delayed post-hypoxic changes in hippocampal tissue slices.